Conventionally, there have been proposed various methods of measuring a specific component in a living body or a specimen such as a solution using an attenuated total reflectance (ATR) measurement device.
A patient with advanced diabetes owns an easy-to-use blood glucose determination device of blood-collecting type so that she can adopt a method of determining a blood glucose level by collecting blood by herself. Recently, however, development in noninvasive measurement is in progress. For example, there has been proposed a method of using an ATR (attenuated total reflectance) prism, in which attenuated total reflection of incident light is repeated at an interface between a reflection surface of the prism and a living body, and then light emitted to the outside of the prism is analyzed. Japanese Laid-Open Patent Publication No. HEI 9-113439 (page 3 and FIG. 1) discloses a measuring method by sandwiching an ATR prism in a mouth or between fingers.
In the method of the above-described publication, evanescent wave (so-called penetrating wave) is applied to a quantitative analysis. As shown in FIG. 4, light 53 propagated through an optical fiber 54 travels in an ATR prism 51 while slightly seeping out, and the seeped light goes into lips 52 and then is reflected. That is, part of the light 53 enters the lips 52 and is affected by components in body fluid existing in the lips 52. For this reason, variations in reflectance and absorptance of the body fluid can be detected by measuring the amount of the reflected light, or returned light. Thereby, information about the components in the body fluid can be obtained.
According to “Fiber Optics User's Manual”, of Spectra-Tech, Version 2.0 (pages 2 and 9), an optical fiber ATR probe 61 as shown in FIG. 5 is disclosed as a form of a prism. When an ATR probe 62 is made contact with a lip 52, light propagated from the light source side (not shown) of an optical fiber 63 through the ATR prove 62 enters the lip 52 and is reflected, and then the reflected light is propagated to the light reception side (not shown) of the optical fiber 63. However, conventional measuring devices as described above have the following problems.
For example, a penetration depth is calculated by a known formula under the conditions that light of 10 microns in wavelength and an ATR prism made of a ZnSe crystal (refractive index: about 2.0) are used, an incident angle is set at 45° and water is used as a surrounding medium (refractive index: about 1.24). The penetration depth obtained herein is 4.7 microns. If the refractive index of the surrounding medium is varied, the penetration depth is also varied. In any event, however, the penetration depth is a few microns at the highest.
In other words, conventional measuring devices allow measurement of information about the surface and its vicinity of the living body. However, if a disturbance layer such as saliva exists between the ATR prism and the subject, light may not reach the living body or the depth of light entering the living body may vary, which makes the obtained signal unstable.
Further, if water and air exist in part of a sensing part of the ATR prism, or water exists on the whole surface of the sensing part of the ATR prism, a spectrum obtained is varied in shape. An intervenient air layer is also a cause of the variation in spectrum.
Therefore, when the ATR prism is sandwiched between the lips to be pressed by them as in the above-described prior art technique, the degree of contact varies depending on a force closing the lips. Accordingly, the contact between the ATR prism surface and the lips becomes unstable and the thickness of the saliva layer becomes difficult to control. Further, due to the influence of an intervenient air layer or the like, measurement data is apt to vary. Even if the saliva layer is wiped off, the contact is insufficient because a oral mucosa has a surface with fine irregularity, and therefore the air layer may exist if the contact is not achieved.
The larger the contact region of the ATR prism is, the more difficult it becomes to realize completely uniform contact. Then, an optical fiber ATR probe 61 as shown in FIG. 5 is considered as the one having a small contact region. The linear ATR probe has a corner 62 which is edged or slightly rounded. Accordingly, when pressed strongly against the lip for contact, the corner may cause pain in the lip contacting thereto. This may weaken the pressing force, resulting in unstable contact.
According to BME, Vol.5, No. 8 (Japanese Society for Medical and Biological Engineering, 1991), there has been proposed a method of measuring a blood glucose level and an ethanol concentration in blood by bringing an ATR element made of an ZnSe optical crystal or the like into contact with a labial mucosa, introducing a laser beam of 9 to 11 microns in wavelength into the ATR element to cause multiple reflection of the laser beam in the inside of the ATR element, and analyzing absorbed light, scattered light or reflected light.
This method allows real-time and noninvasive measurement of a concentration of a specific component such as glucose, ethanol or cholesterol. Also in this method, evanescent wave (penetrating wave) is applied to the quantitative analysis.
Light traveling in the ATR element slightly gets into the lips and is affected by components contained in a body fluid existing there. For example, glucose shows a light absorption peak at a light wave number of 1080 cm−1.
Therefore, if light of this wave number is applied to a living body, the amount of light absorption varies depending on variations in glucose concentration in the living body. Thus, variations in light absorption due to variations in concentration of body fluid components are detected by measuring light returned from the living body, thereby obtaining a concentration of each component.
In general, however, the ATR measurement device is used for surface analysis of a substance and an incident angle of 45° is adopted in most cases. Therefore, the depth to which the evanescent wave enters is almost at the same level as the wavelength, i.e., the light passes only a small distance in the living body.
Accordingly, an optical path of light passing through the body fluid is extremely short and hence the amount of light absorbed in the body fluid is very small. Therefore, a sufficiently large signal strength cannot be obtained by a single total reflection.
For this reason, there has been attempted to increase the signal strength by repeating the total reflection. However, in order to reflect the light many times, the element itself needs to be upsized, which is problematic because the cost of the optical element increases. Further, as a result of the upsizing of the element, the region to be measured becomes large, and hence it becomes relatively difficult to obtain a signal from a region which is truly required to be measured.
In view of the foregoing points, a first object of the present invention is to provide a biological attribute measuring method and a biological attribute measuring device that allow highly accurate measurement by easily bringing a prism comprising a contact device into contact with a measuring region.
Further, a second object of the present invention is to provide a biological attribute measuring method and a biological attribute measuring device for measuring a concentration of a specific component by obtaining a large measurement signal with a small optical element.